The effects of adding Carbicarb--a 50:50 mixture of sodium bicarbonate (NaHCO3) and sodium carbonate (Na2CO3)--or sodium bicarbonate or disodium carbonate individually to whole blood were examined in vitro. Adding HCl to blood in an open system rapidly decreased the pH and [HCO3-] without increasing partial pressure of carbon dioxide (PCO2), whereas adding HCl to blood in a closed system markedly decreased pH and increased PCO2. Adding sodium bicarbonate to blood caused a rapid and predictable increase in PCO2 that was linearly related to the pH of the blood at the time of addition. Adding disodium carbonate to blood caused a rapid and predictable fall in PCO2 that was linearly related to the initial PCO2 of the blood at the time of addition. Adding Carbicarb to blood caused relatively little change in PCO2 over a wide range of initial pH and PCO2 values.